Dyslipidemia
Conditions
Keywords
LDL-C, Hypercholesterolemia, Cholesterol absorption inhibitor, ATP-citrate lyase inhibitor
Brief summary
The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Detailed description
This is a randomized, single-blind, placebo-controlled study in healthy participants with elevated low-density lipoprotein-cholesterol (LDL-C). This study will assess the pharmacokinetic (PK), safety, tolerability, and efficacy of AZD0780 in combination with ezetimibe, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid. Participants will be randomized to receive either AZD0780 or placebo (to be administered with ezetimibe, ezetimibe/rosuvastatin, or ezetimibe/bempedoic acid). The study will comprise: 1. A Screening Period of up to 28 days. 2. A Run-in Period of 28 days. 3. A Treatment Period of 28 days. 4. Two Follow-up Visits, one and two weeks after the last dose of study drug.
Interventions
DRUGAZD0780
AZD0780 tablet will be administered orally.
DRUGEzetimibe
Ezetimibe tablet will be administered orally.
DRUGRosuvastatin
Rosuvastatin tablet will be administered orally.
DRUGBempedoic Acid
Bempedoic Acid tablet will be administered orally.
DRUGPlacebo
Placebo will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Signed the informed consent form before any study-related procedure. 2. All females must have a negative serum pregnancy test at the Screening Visit and on admission to the Clinical Unit 3. Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: postmenopausal or surgically sterilized females. 4. Have a Body Mass Index (BMI) \> 18 kg/m² and weigh at least 50 kg. 5. Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods. 6. Fasting LDL-C \> 100 mg/dL but \< 190 mg/dL (\> 2.6 mmol/L but \< 4.9 mmol/L for London EPCU) at the Screening Visit. 7. Fasting triglycerides \< 400 mg/dL (or \< 10.3 mmol/L for London EPCU) at the Screening Visit.
Exclusion criteria
1. History of any clinically important disease or disorder. 2. History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention. 4. Any laboratory values with specific deviations in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBL), estimated glomerular filtration rate, or hemoglobin at the Screening Visit or on Admission 5. Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results other than those described under exclusion criterion number 4, at Screening and/or Admission to the Clinical Unit 6. Any positive result on Screening for serum HBsAg, hepatitis B core antibody or human immunodeficiency virus. 7. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0780, ezetimibe, rosuvastatin, and bempedoic acid. 8. Treatment with any lipid-lowering therapy or AZD0780 within the 3 months prior to Screening. 9. Treatment with drugs for reduction or inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) within the last 12 months prior to Screening (approved or investigational and apart from AZD0780).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in direct Low-density Lipsprotein Cholesterol (LDL-C) | Week 4 | To evaluate the effect of AZD0780 on LDL-C levels versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Number of participants with adverse events | From screening (Day -56 to -29) to 14 Weeks | The safety and tolerability of AZD0780 when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under concentration-time curve in the dosing interval (AUCtau) (Day 15) | From Day 1 to Day 42 | To further characterize AZD0780 PK in plasma. |
| Maximum observed drug concentration (Cmax) | From Day 1 to Day 42 | To further characterize AZD0780 PK in plasma. |
| Time to reach maximum observed concentration (tmax) | From Day 1 to Day 42 | To further characterize AZD0780 PK in plasma. |
| Change from baseline in LDL-C ultra | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in LDL-C Friedewald | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Plasma concentration of AZD0780 | From Day 1 to Day 42 | To further characterize AZD0780 pharmacokinetics (PK) in plasma. |
| Change from baseline in non- HDL-C (high-density lipoprotein-cholesterol) | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in HDL-C | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in triglycerides | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in in Lipoprotein A [Lp(a)] | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in Apolipoprotein B (ApoB) | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Change from baseline in total cholesterol | Week 4 | To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid. |
| Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) | From Day 1 to Day 42 | To further characterize AZD0780 PK in plasma. |
Countries
United Kingdom, United States
Outcome results
None listed